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. 2014 Nov 17;124(12):5503–5515. doi: 10.1172/JCI74119

Figure 7. MSCs transiently acquire the gene expression of liver progenitor cells during their differentiation into hepatocytes.

Figure 7

(A–O) Freshly isolated HSCs, clonally expanded HSCs (clones 1E7, 4E7, and 3F8), BM MSCs, and UCBSCs (clone 1G11) from rats were treated for 21 days with a hepatocyte differentiation medium that contained HGF and FGF4. Expression of (A) vimentin, (B) desmin, (C) K19, (D) Epcam, (E) Lgr5, (F) α-fetoprotein, (G) Cyp7a1, (H) Hnf4a, (I) albumin, and (J) Sox9 was analyzed by qPCR. mRNA samples were taken at weekly intervals. Gene expression of the cells at the beginning of the differentiation experiments is indicated as Day 1. (K) To verify hepatic differentiation, the hepatocyte marker albumin was also measured in the culture supernatant of HSCs, HSC clones, BM MSCs, and UCBSCs by a rat-specific albumin ELISA. Hepatic function of MSC-derived hepatocyte-like cells was also determined by quantitation of the bile acids (L) cholic acid, (M) chenodeoxycholic acid, (N) ursodeoxycholic acid, and (O) ω/α-muricholic acid in culture supernatants by UHPLC-MS/MS. Bile acids were allowed to accumulate for 2 days in the culture medium before analysis. Bar values represent arithmetic means and were interpolated to indicate the trend (colored lines) for each cell group. Expression profiles, albumin synthesis, and bile acid release were determined in 3 independent experiments (n = 3).